End stage renal disease (ESRD) is a devastating consequence of progressive renal failure that sharply reduces both the quality of life and life expectancy. The mental and physical costs to the patients with ESRD are incalculable and the financial cost of medical care in 1990 exceeded 3 billion dollars. Hypertensive nephrosclerosis is believed to be responsible for 25 % of cases of ESRD in the United States. Furthermore, it is the most common cause of ESRD in blacks who suffer a disproportionately (3-20 fold) greater incidence of renal failure from hypertension as compared to non-blacks. Lowering blood pressure (BP) with antihypertensive drugs has been shown to slow the rate of progression of renal failure. However, despite controlling diastolic blood pressure in the 90-100 mm Hg range, approximately 20% of patients have unrelenting, progressive renal failure within 4-6 years of follow-up. Two major questions in this field remain unanswered: 1) does lowering diastolic blood pressure below conventional control levels preserve renal -function better than conventional blood pressure control?; and 2) do newer antihypertensive agents protect the kidney better than conventional antihypertensive agents? Therefore, the goal of this proposal is to design and carry out a pilot study in which 100 patients with hypertensive nephrosclerosis and renal insufficiency (GFR equal to or less than 75 ml/min/ 1.73 M(2)) are assigned to either strict (diastolic BP 70-80 mm Hg) or usual (diastolic BP 85-95 mm Hg) BP control and treated with one of three BP medications: 1) Fosinopril; 2) Isradepine; or 3) Atenolol, in a double-blind, randomized fashion. Renal function will be assessed by serial measurement of glomerular filtration rate over a 12 month period. Hypertensive nephrosclerosis will be diagnosed by renal biopsy. The pilot study will be limited to black patients because of their extreme high risk for progressive renal failure. It will serve as a basis for designing a large-scale trial to determine whether Fosinopril or Isradepine are both safe and more efficacious than Atenolol in slowing the rate of progression of established renal disease in hypertensive nephrosclerosis. This study may provide a means by which the incidence of ESRD in this high risk population can be effectively forestalled or prevented altogether.
